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J Kraan

Publications and source records attributed to J Kraan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Analysis of variation in results of CD34+ hematopoietic progenitor cell enumeration in a multicenter study.

A workshop was held in The Netherlands and Belgium with the aim of investigating whether or not the use of a standard protocol vs. local protocols for flow cytometric enumeration of CD34+ hematopoietic progenitor cells would reduce interlaboratory variation. The standard protocol consisted of a three-color, whole-blood staining technique based on fluorescein isothiocyanate (FITC)-labeled CD34, and phycoerythrin (PE)-labeled CD14 and CD66e monoclonal antibodies (reactive with monocytic and myeloid cells, respectively), followed by erythrocyte lysis, washing, fixation, and selection of nucleated cells during data acquisition on the basis of their positivity for LDS-751 (staining DNA and RNA). Data analysis guidelines included the elimination of nonspecific antibody binding by monocytes and myeloid cells by gating on the CD14-, 66e- cells, followed by setting a window on a CD34 vs. sideward light scatter (SSC) plot around the CD34+, SSClow cells. The FITC-labeled isotype control was analyzed with the same gate and window settings, and the false-positive events were subtracted from CD34 result. Four samples (i.e., peripheral blood and apheresis product from two patients) were sent out. Results were received on patient 1 (2) from 36 (38) laboratories. Data obtained by 24 (26) laboratories after correct application of the standard protocol revealed that the median percentage of CD34+ cells of the four samples ranged between 1.1% and 3.7% and the CVs between 18% and 30%. Incorrect performance of the standard protocol by 12 laboratories, mainly resulting from gating errors, yielded a larger variation (CVs ranging between 50% and 82%). CD34 enumeration using local protocols by 29 (34) laboratories yielded median percentage of CD34+ cells ranging between 1.2% and 3.9% and CVs ranging between 34% and 106%. We conclude that correct application of this standard protocol was effective in reducing the interlaboratory variation in percentage of CD34+ cells assessments.

Antibodies, Monoclonal↗
PubMed1997

Reduction of interlaboratory variability in flow cytometric immunophenotyping by standardization of instrument set-up and calibration, and standard list mode data analysis.

Two workshops addressed the question to which degree standardization of instrument set-up and calibration, and standard list mode data analysis would reduce interlaboratory variability of flow cytometric results on prestained peripheral blood mononuclear cells (PBMC). Standard instrument set-up included uniform positioning of the "windows of analysis" for the forward and sideward light scatter and fluorescence (FL) 1 (i.e., fluorescein isothiocyanate [FITC]) and 2 (i.e., phycoerythrin [PE]) parameters. Reference standards and PBMC, double-stained with FITC- and PE-conjugated monoclonal antibodies covering a wide range of FL intensities and coexpression patterns, were sent out to 25 laboratories in Workshop 1 and to 35 laboratories in Workshop 2 with the following requests: a) to set up instruments according to local and standard protocols, b) to acquire list mode data on the PBMC with both instrument settings, and c) to analyze both datasets according to local protocols. Standard analysis of the list mode data acquired with uniform instrument settings was performed centrally using so-called "latent class model" software (Van Putten et al., Cytometry 14:86-96, 1993). This software provides an automated, "no-gating" analytical method of lymphocyte immunophenotypes and employs fixed FL marker settings as defined prior to each analytical run. In Workshop 1, these markers were set in identical histogram channels for all instruments based on results obtained with a reference instrument. Standard analysis of list mode data acquired after uniform instrument set-up led only to a 13% reduction of interlaboratory variability of results as compared to data analysis using local protocols. The standard protocol for instrument set-up led to uniform positioning of relatively strong FL signals but variable positioning of unstained cells on the FL histogram scales. Hence, standard FL marker settings were inappropriate for some instruments. Therefore, instrument responses to FITC and PE signals in Workshop 2 were calibrated using microbeads labeled with FITC or PE in a range of predefined FL intensities expressed in MESF units (molecules of equivalent soluble fluorochrome). That approach allowed the positioning of the FL markers for the standard analysis on the basis of identical FL1 and FL2 intensities, expressed in MESF units, for all instruments. Standard analysis of list mode data acquired after uniform instrument set-up and calibrated FL marker settings led to a 43% reduction of interlaboratory variability as compared to data analysis to local protocols. We conclude that standard list mode data analysis using fixed FL marker settings reduces the interlaboratory variability of flow cytometric results on prestained PBMC, provided that the instruments have been set up in a uniform way and that FL markers have been standardized on the basis of calibration of each instrument's response to the corresponding FL signals.

Antigens, CD↗
PubMed1997

Stereoselective synthesis and biodistribution of potent [11C]-labeled antagonists for positron emission tomography imaging of muscarinic receptors in the airways.

Quantitation of muscarinic receptors in the lungs in vivo with positron emission tomography (PET) is of clinical interest. For that purpose we decided to develop [11C]-labeled ligands with a high affinity (KD < 0.1 nM). Three quaternary muscarinic antagonists, racemic N-methylpiperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 1a (pKB = 10.39), its (R)-isomer 1b (pKB = 11.08), and (R,R)-quinuclidin-3-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 2 (pKB = 11.28), were labeled by reacting [11C]CH3I with their tertiary amine precursors. The enantiomerically pure tertiary amine precursors were prepared by stereoselective synthesis starting from (R)-(-)-mandelic acid. In vitro binding assay of 1b and 2 demonstrated that both ligands bind with very high affinity to the muscarinic receptor subtypes M1, M2, and M3. They are more potent than the muscarinic antagonist (R)-N-methylquinuclidinyl benzilate ((R)-MQNB). Distribution studies with 1a, 1b, and 2 in control and atropine-treated male Wistar rats demonstrated significant specific binding (90-99% of total issue uptake) in tissues containing cholinoceptors (heart, intestine, lung, pancreas, spleen, stomach, submandibular gland). Because the tissue/plasma concentration ratios of 1b are most favorable, this ligand was used for further evaluation. Analysis of plasma samples showed a very rapid clearance (t1/2 = 0.3 min) of the radioligand 1b and a relatively slow appearance of a hydrophilic metabolite. At 15 min postinjection of 1b, analysis of heart, lungs, and liver showed that respectively 99%, 88%, and 8% of the tissue radioactivity corresponded with the parent compound. Ligand 1b appears to be an excellent candidate for PET studies of mAChR receptors in heart and lungs.

Animals↗
PubMed1997

Characterization of pulmonary and myocardial beta-adrenoceptors with S-1'-[fluorine-18]fluorocarazolol.

UNLABELLED: S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its potential for noninvasive measurement of regional pulmonary and myocardial beta-adrenoceptor densities. METHODS: High-specific activity fluorocarazolol was intravenously injected on two separate occasions within a 1-wk interval. The initial injection was without pretreatment, but before the second injection, the volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time frames of 31 planes were acquired over a period of 60 min after each injection. Blood samples were drawn and analyzed for the presence of fluorocarazolol and radioactive metabolites. RESULTS: Uptake of fluorocarazolol in the target tissues was hardly affected by salbutamol but was strongly depressed by pindolol. Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50 min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after treatment with pindolol. CONCLUSION: These data indicate that: 1. Pulmonary and myocardial uptake of radioactivity after intravenous administration of S-1'-[18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2. Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle under these conditions. 3. Binding kinetics do not preclude quantification of receptors with compartment models.

Adrenergic beta-Agonists↗
PubMed1997

Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.

UNLABELLED: We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. METHODS: The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. RESULTS: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. CONCLUSION: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.

Adrenergic beta-Antagonists↗
PubMed1997

Techniques in human airway inflammation: differences in plastic-embedded and snap-frozen sections for CD3, CD4, and CD8 immunostaining of bronchial biopsy specimens.

Today, the quantification of inflammatory cells in human airway biopsies might be facilitated by better morphologic resolution provided by special resin (plastic)-embedding techniques. The present study compares the numbers of CD3-, CD4-, and CD8-positive cells in glycolmethacrylate-embedded versus snap-frozen biopsy specimens of normal bronchial mucosa in 10 patients with various pulmonary diseases. In general, larger numbers of CD3-, CD4-, and CD8-positive cells were counted in snap-frozen specimens than in plastic-embedded ones. Loss of antigenic properties during storage of plastic-embedded tissue (blocks) might have contributed to the weak correlation between both methods. An additional study showed that the number of CD3-, CD4-, and CD8-positive cells decreased significantly within a few months after embedding in glycolmethacrylate. Therefore, we recommend processing glycolmethacrylate-embedded specimens as soon as possible. For standard evaluation of established inflammatory cell parameters such as CD3, CD4, CD8, and EG2, frozen tissue is preferable because of the ease of the method and its reliable cell counting. Because glycolmethacrylate-embedded tissue shows superior morphologic resolution, under strict rules, this method seems attractive for the study, in particular, of cell-cell and cell-matrix relationships.

Biopsy↗
PubMed1996

Long-term effects of home rehabilitation on physical performance in chronic obstructive pulmonary disease.

A pilot study was set up to assess the long-term effects of once weekly versus once monthly follow-up of pulmonary rehabilitation after a comprehensive home rehabilitation program on physical performance in patients with chronic obstructive pulmonary disease (COPD) during an 18-mo period. Thirty-six patients with a mean FEV1 of 1.3 +/- 0.4 L (43% pred) were included in the study. Groups A and B (n = 23) visited the physical therapist twice weekly for 3 mo. Thereafter, 11 patients (Group A) had a follow-up of pulmonary rehabilitation once a week, and 12 patients (Group B) had a follow-up once a month. Thirteen patients received no rehabilitation at all (Group C). Long-term home rehabilitation does not appear to improve exercise tolerance; however, on the other hand, there is a deterioration in vital capacity (p < 0.01), walking distance (p < 0.01), and maximal work load (p < 0.05), as shown in the control group. A small improvement in exertional dyspnea (p < 0.01) after 18 mo and inspiratory muscle function (p < 0.05) after 12 mo was shown only in Group A. Because of the insufficient number of patients enrolled in this pilot study, no clear benefit on physical performance of long-term home rehabilitation with either weekly or monthly supervision could be demonstrated.

Exercise Test↗
PubMed1996

Effects of home rehabilitation on physical performance in patients with chronic obstructive pulmonary disease (COPD).

We investigated whether 12 weeks of rehabilitation at home in patients with chronic obstructive pulmonary disease (COPD) had a beneficial effect on lactate production, metabolic gas exchange data, workload of the inspiratory muscles, and dyspnoea during a maximal bicycle ergometer test. A second aim was to assess whether a change in dyspnoea was related to a change of inspiratory muscle workload. Forty three COPD patients with severe airways obstruction were included in the study: mean forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 L (44% predicted), mean FEV1/inspiratory vital capacity (IVC) 37 +/- 8%. Twenty eight patients started a rehabilitation programme, whilst 15 patients received no rehabilitation. Rehabilitation was carried out at home; patients were supervised by a general practitioner, a physiotherapist and a nurse. Exercise tolerance was measured by means of a 6 min walking distance test (6MWD) and maximal workload (Wmax) during an incremental symptom-limited cycle ergometer test. Inspiratory muscle workload at Wmax was assessed with the Tension Time Index (TTI), and dyspnoea at Wmax with the Borg scale. After 12 weeks, the rehabilitation group showed a significantly larger increase in 6MWD (from 438 to 447 m) and in Wmax (from 70 to 78 W) compared with the control group. A significant improvement in oxygen consumption (V1O2) (from 1.0 to 1.1 L), lactate level (from 3.7 to 3.1 mEq.L(-1)), dyspnoea (from 6.0 to 4.5) and TTI (from 0.10 to 0.08) at Wmax occurred in the rehabilitation group during the programme. The reduction in TTI was not significantly correlated with the fall in dyspnoea, as assessed by the Borg scale. We conclude that 12 weeks of rehabilitation at home in COPD patients increases symptom-limited V1O2 in combination with an increased Wmax. At this significantly higher Wmax, there was a reduction in dyspnoea, lactate level and inspiratory muscle workload. The reduction in dyspnoea was not related to a decreased inspiratory muscle workload. This study shows that rehabilitation at home can produce beneficial physiological improvements during exercise in patients with chronic obstructive pulmonary disease.

Aged↗
PubMed1995

Effect of casein-based semi-synthetic food on renal acid excretion and acid-base state of blood in dogs.

Urinary acid excretion and blood acid-base state were determined in dogs fed a casein-based semi-synthetic food (SSF), to which different amounts of salts had been added, in comparison with feeding normal dog food. Net acid excretion (NAE) and inorganic acid excretion (IAE) increased during SSF feeding. IAE was higher than the acid load calculated from the sulphur and phosphorus content of the casein. This higher IAE appeared to be due to the presence of calcium and magnesium phosphate in the diet, because calcium and magnesium may be in part precipitated as carbonate, leaving phosphate to be absorbed as phosphoric acid. Acid excretion decreased by addition of CaO. When no neutral Na+ and K+ salts were added, the increase in NAE was accompanied by a metabolic acidosis. K+ was more effective in attenuating the acidosis than Na+. On the basis of these findings a diet can be made which imposes a known acid load, and provides stable baseline values. Hence, any additions that influence the acid-base balance can be properly studied. The data obtained in these and future studies utilising this diet may be of help in optimising the composition of nutrient solutions to be used in the care of critically ill patients.

Absorption↗
PubMed1995

Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.

BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease (COPD). However, appropriately controlled studies have not previously been performed, nor have the benefits of different types of continuation programme for rehabilitation been investigated. Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty six patients with severe airways obstruction (mean SD) forced expiratory volume in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC) 37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner. During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11 patients (group A) received a session of physiotherapy once weekly while 12 patients (group B) received a session of physiotherapy once a month. The control group C (13 patients) received no rehabilitation at all. Quality of life was assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six minute walking distance, and lung function by FEV1 and IVC. Outcome measures were assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term improvements in quality of life were found in patients in groups A and B, but not in those in group C compared with baseline, but these only reached significance in group B at all time points. Patients in group B had a higher quality of life than those in group C only at three and 12 months. There was a decrease in both six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18 months) in patients in group C compared with the baseline measurement. Between groups analysis showed no differences for six minute walking distance, FEV1, and IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months. The change in quality of life was not associated with a change in exercise tolerance.

Exercise Tolerance↗
PubMed1994

Reliability and validity of the chronic respiratory questionnaire (CRQ).

BACKGROUND: The Chronic Respiratory Questionnaire (CRQ) is frequently applied to assess quality of life in patients with chronic obstructive pulmonary disease (COPD). However, the reliability and validity of this questionnaire have not yet been determined. This study investigates the reliability and validity of the four separate dimensions of the CRQ. METHODS: The CRQ was administered on two consecutive days to 40 patients with COPD (mean FEV1 44% predicted, FEV1/IVC 37% predicted). Internal consistency reliability of each dimension was investigated by Cronbach's alpha reliability coefficient, test retest reliability by the Spearman-Brown reliability coefficient (p), and content validity by Pearson's correlation coefficient between the CRQ and the symptom checklist (SCL-90). RESULTS: Items of the fatigue, emotion, and mastery dimensions showed a high internal consistency reliability (alpha = 0.71-0.88) as well as a high test retest reliability (p above 0.90). These three dimensions correlated with comparable dimensions of the SCL-90. Items of the dyspnoea dimension showed a low internal consistency reliability (alpha = 0.53) and a test retest reliability of p = 0.73. CONCLUSIONS: Items of the dimensions fatigue, emotion, and mastery of the CRQ are reliable and valid and can be used to assess quality of life in patients with severe airways obstruction. Items of the dyspnoea dimension are less reliable and should not be included in the overall score of the CRQ in comparative research. However, by scoring the items of dyspnoea separately they may be useful for the evaluation of the effects of intervention in a specific patient.

Aged↗
PubMed1994

Relation of lung function, maximal inspiratory pressure, dyspnoea, and quality of life with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Several studies have shown that both objective and subjective measurements are related to exercise capacity in patients with chronic obstructive pulmonary disease (COPD). In this study the relative contribution of lung function, maximal inspiratory pressure, dyspnoea, and quality of life to the performance in a walking distance test and a bicycle ergometer test was investigated. METHODS: Static lung volumes, forced expiratory volume in one second (FEV1), inspiratory slow vital capacity (IVC), transfer factor for carbon monoxide (TLCO) divided by the alveolar volume (TLCO/VA), static compliance (Cst), and maximal inspiratory peak pressure (PImaxPOES) were measured in 40 patients with COPD with severe airways obstruction (mean FEV1 44% predicted, mean FEV1/IVC 37% predicted). Quality of life was assessed by the Chronic Respiratory Questionnaire (CRQ) and dyspnoea by the Borg category scale. Exercise capacity was measured by both a six minute walking distance (test) and a maximal work load of the bicycle ergometer test (Wmax). RESULTS: Spirometric values and maximal inspiratory pressure were modestly correlated with both the six minute walking test and Wmax, r values ranging from 0.50 to 0.58. The TLCO was strongly correlated with the six minute walking test (r = 0.62) and with Wmax (r = 0.78). Quality of life showed no correlation with exercise capacity, while there was a correlation between dyspnoea and the six minute walking test (r = -0.41). Backward linear regression analysis selected TLCO and PImaxPOES as the most significant determinants for exercise performance. They explained 54% and 69% of the variance in the six minute walking test and Wmax, respectively. CONCLUSIONS: The results show that exercise capacity in patients with COPD with severe airways obstruction is more strongly related to inspiratory muscle strength and lung function than to dyspnoea and quality of life. The significant correlation between dyspnoea and the six minute walking test suggests that subjective variables are more strongly related to walking tests than to bicycle ergometer tests.

Aged↗
PubMed1994

Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.

We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.

Breathing Exercises↗
PubMed1991

Late onset asthma?

A 77 yr old male was referred for dyspnoea and recurrent infections of the lower airways for the previous five months. On the lateral chest roentgenogram a process in the tracheal area was found, and during bronchoscopy a polypoid tumour was seen about four centimetres above the main carina. It appeared to be a benign endotracheal tumour which was removed after coagulation by a Neodymium yttrium aluminium garnet (YAG) laser.

Age Factors↗
PubMed1989

Changes in maximum expiratory flow-volume curve configuration after treatment with inhaled corticosteroids.

The present study reports the changes in configuration of maximal flow-volume curves after eight weeks' treatment with inhaled corticosteroids in 14 asthmatic patients. The configuration was compared with that seen after bronchodilatation following inhalation of a single dose of ipratropium bromide. After inhaled corticosteroids the shape of the flow-volume curves was less bowed toward the volume axis, whereas the shape of the flow-volume curves after inhalation of ipratropium bromide showed no significant change. A significant correlation was observed between the decrease in blood eosinophil cell count and the straightening of the flow-volume curves, quantitatively expressed as shape factor and slope ratio. It is concluded that these changes in flow-volume curve configuration reflect a decrease in inhomogeneously distributed inflammatory airway narrowing.

Adolescent↗
PubMed1989

Effect of theophylline and enprofylline on bronchial hyperresponsiveness.

The effect of increasing intravenous doses of theophylline and enprofylline, a new xanthine derivative, on bronchial responsiveness to methacholine was studied in eight asthmatic patients. Methacholine provocations were carried out on three days before and after increasing doses of theophylline, enprofylline, and placebo, a double blind study design being used. Methacholine responsiveness was determined as the provocative concentration of methacholine causing a fall of 20% in FEV1 (PC20). The patients were characterised pharmacokinetically before the main study to provide an individual dosage scheme for each patient that would provide rapid steady state plasma concentration plateaus of 5, 10, and 15 mg/l for theophylline and 1.25, 2.5, and 3.75 mg/l for enprofylline. Dose increments in the main study were given at 90 minute intervals. FEV1 showed a small progressive decrease after placebo; it remained high in relation to placebo after both drugs and this effect was dose related. Methacholine PC20 values decreased after placebo; mean values were higher after theophylline and enprofylline than after placebo (maximum difference 2.0 and 1.7 doubling doses of methacholine); the effect of both drugs were dose related. Thus enprofylline and theophylline when given intravenously cause a small dose related increase in FEV1 and methacholine PC20 when compared with placebo.

Adult↗
PubMed1988

The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease.

We have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances. Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml.h-1.kg-1 respectively. Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml.h-1.kg-1 respectively. There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance. It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.

Adult↗